ABBV-467 / AbbVie - LARVOL DELTA

Enabling, Decagram-Scale Synthesis of Macrocyclic MCL-1 Inhibitor ABBV-467. (PubMed, J Org Chem) - "Herein, we describe the synthesis of ABBV-467 on a decagram scale, which enabled preclinical characterization. The strategy is convergent and stereoselective, featuring a hindered biaryl cross coupling, enantioselective hydrogenation, and conformationally preorganized macrocyclization by C-O bond formation as key steps."

Journal • Hematological Malignancies • Multiple Myeloma • Oncology

Selective MCL-1 inhibitor ABBV-467 is efficacious in tumor models but is associated with cardiac troponin increases in patients. (PubMed, Commun Med (Lond)) - P1 | "The selectivity of ABBV-467 suggests that treatment-induced troponin release is a consequence of MCL-1 inhibition and therefore may represent a class effect of MCL-1 inhibitors in human patients."

Journal • Preclinical • Acute Myelogenous Leukemia • Hematological Disorders • Leukemia • Lymphoma • Multiple Myeloma • Oncology • BCL2 • TNNI3

NA1-115-7, from Zygogynum pancheri, is a new selective MCL-1 inhibitor inducing the apoptosis of hematological cancer cells but non-toxic to normal blood cells or cardiomyocytes. (PubMed, Biomed Pharmacother) - "Synthetic inhibitors targeting these proteins have been developed, and some hematological malignancies are now widely treated with a BCL-2 inhibitor (venetoclax)...Six MCL-1 inhibitors (S64315, AZD-5991, AMG-176, AMG-397, ABBV-467 and PRT1419) have been evaluated in clinical trials since 2016, but some were affected by safety issues and none are currently used clinically...Importantly, a similar treatment with NA1-115-7 was not toxic to erythrocytes, peripheral blood mononuclear cells, platelets, or cardiomyocytes. These results highlight the potential of natural products for use as specific BH3 mimetics non-toxic to normal cells, and they suggest that NA1-115-7 may be a promising tool for use in cancer treatment."

IO biomarker • Journal • Hematological Disorders • Hematological Malignancies • Lymphoma • Oncology • BCL2L1

A Study of the Safety and Tolerability of ABBV-467 in Adult Participants With Relapsed/Refractory (R/R) Multiple Myeloma (clinicaltrials.gov) - P1; N=8; Terminated; Sponsor: AbbVie; Trial completion date: Jun 2023 ➔ Apr 2021; Active, not recruiting ➔ Terminated; Trial primary completion date: Jun 2023 ➔ Apr 2021; Strategic considerations

Clinical • Trial completion date • Trial primary completion date • Trial termination • Hematological Malignancies • Multiple Myeloma • Oncology

A Study of the Safety and Tolerability of ABBV-467 in Adult Participants With Relapsed/Refractory (R/R) Multiple Myeloma (clinicaltrials.gov) - P1; N=8; Active, not recruiting; Sponsor: AbbVie; Recruiting ➔ Active, not recruiting

Enrollment closed • Hematological Malignancies • Multiple Myeloma • Oncology

A Study of the Safety and Tolerability of ABBV-467 in Adult Participants With Relapsed/Refractory (R/R) Multiple Myeloma (clinicaltrials.gov) - P1; N=108; Recruiting; Sponsor: AbbVie; N=54 ➔ 108

Clinical • Enrollment change • Hematological Malignancies • Multiple Myeloma • Oncology • CD38

A Study of the Safety and Tolerability of ABBV-467 in Adult Participants With Relapsed/Refractory (R/R) Multiple Myeloma (clinicaltrials.gov) - P1; N=54; Recruiting; Sponsor: AbbVie; N=108 ➔ 54

Clinical • Enrollment change • Hematological Malignancies • Multiple Myeloma • Oncology

A Study of the Safety and Tolerability of ABBV-467 in Adult Participants With Relapsed/Refractory Multiple Myeloma (clinicaltrials.gov) - P1; N=108; Recruiting; Sponsor: AbbVie; Not yet recruiting ➔ Recruiting; N=54 ➔ 108; Initiation date: Nov 2019 ➔ Apr 2020

Enrollment change • Enrollment open • Trial initiation date • Hematological Disorders • Hematological Malignancies • Multiple Myeloma • Oncology

Newly added product (clinicaltrials.gov) - P1, Oncology

Pipeline update